tbuckley/cabot-search huggingface dataset:
Late Preterm Birth and the Risk of Cardiometabolic Disease
Authors: Lauren Iacono, Molly O. Regelmann
Journal: JAMA Network Open (2022)

Yulika Yoshida-Montezuma, MPH; Branavan Sivapathasundaram, MPH; Hilary K. Brown, PhD; Charles Keown-Stoneman, PhD; Russell J. de Souza, RD, ScD; Teresa To, PhD; Cornelia M. Borkhoff, PhD; Catherine S. Birken, MD, MSc; Jonathon L. Maguire, MD, MSc; Laura N. Anderson, PhD
DIPG-29. Highly multiplexed digital spatial profiling of the tumor immune environment of pediatric and adult<i>H3 K27M</i>-mutant diffuse midline gliomas
Authors: Sudarshawn Damodharan, Jeffrey Helgager, Mahua Dey
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: H3 K27M-mutant diffuse midline gliomas (DMGs) are highly aggressive malignancies of the central nervous system that affect both pediatric and adult populations. The immune layout and genetic changes within the tumor microenvironment associated with these high-grade malignancies are thought to play an integral role in the phenotypic differences in tumor presentation and clinical course between both populations. Comparative immune landscape between pediatric and adult DMGs is not known. METHODS: The NanoString GeoMxTM Digital Spatial Profiler platform was used to determine the immune marker and genetic layout in a cohort of both pediatric and adult H3 K27M-mutant DMG tissue samples. Three fluorescently labeled antibodies targeting immune cells (CD45), epithelial cells (PanCK), tumor cells (H3 K27M) and a nucleic acid stain (SYTO-13) were used to identify and separate out the various components within the tumor tissues from selected regions of interest. The resultant information was then pooled into libraries that were run through the Illumina sequencing system to assess gene expression and proteomics for both cohorts of samples. RESULTS: Our data revealed that there were immune and genetic marker changes that were seen within both populations across multiple regions of interest within the tumor tissues. A number of immune cell types and protein markers exhibited significant difference between the pediatric and adult tissue cohorts. CONCLUSION: The digital spatial analysis of pediatric and adult H3 K27M-mutant DMGs show different immune and genetic profiles which are proposed to contribute to the clinical differences between both populations. These observed differences may play a role in future treatments for H3 K27M-mutant DMGs and further research is needed to explore this.
Thulium fiber vs. thulium yag laser effect on upper urinary tract soft tissue: An ex vivo study
Authors: M.P. Pavia, S. Proietti, L. Rico, L. Blas, R. Lucianò, N.P. Tenace, P. Contreras, A.B. Galosi, F. Gaboardi, G. Giusti
Journal: European Urology (2022)
Detection of presumed germline pathogenic variants of hereditary breast cancer predisposition genes in circulating tumor DNA: SCRUM-Japan MONSTAR-SCREEN.
Authors: Masaya Hattori, Yoichi Naito, Takashi Yamanaka, Hiroyuki Yasojima, Rikiya Nakamura, Junichiro Watanabe, Tetsuhiro Yoshinami, Yukinori Ozaki, Takao Fujisawa, Yoshiaki Nakamura, Hideaki Bando, Takayuki Yoshino, Rui Yamaguchi, Issei Imoto, Hiroji Iwata
Journal: Journal of Clinical Oncology (2022)

1029 Background: Approximately 5-10% of breast cancer are hereditary. Variant allele frequency (VAF) of hereditary breast cancer predisposition genes in circulating tumor DNA (ctDNA) may be useful for detecting presumed germline pathogenic variants. Methods: One hundred and sixty-eight patients with advanced breast cancer (ABC) who underwent ctDNA and tumor tissue sequencing analyses in the SCRUM-Japan MONSTAR-SCREEN, a cancer genome screening project in Japan, from December 2019 to November 2021 were included. The patients were tested and monitored for their genomic alterations by FoundationOne Liquid assay or FoundationOne Liquid CDx assay. The pathogenic variants (PV) of hereditary breast cancer predisposition genes with VAF of 30% or higher in ctDNA were defined as PGPV. The VAF of BRCA1/2 on ctDNA analyses in BRCA1/2 germline pathogenic variant (GPV) carriers and the prevalence of PGPV in five hereditary breast cancer predisposition genes, including ATM, BRCA1, BRCA2, CHEK2, and PALB2, were investigated. Results: From 168 patients with ABC, including 115 Luminal, 32 HER2-positive, and 21 triple negative breast cancer, with a median age of 58 years, 39 PVs in 5 genes were identified with a median VAF of 0.62% (range: 0.1-84.77). ctDNA identified GPV of known BRCA1/2 GPV carriers (1 with BRCA1 and 6 with BRCA2) , with a median VAF of 51.4% (range: 48.2-77.5). The VAF of GPV on ctDNA were higher than 30% in subsequent consecutive samples. Among 161 patients with ABC, excluding 7 known BRCA1/2 GPV carriers, 6 PGPV (1 with BRCA1, 3 with BRCA2, and 2 with PALB2) were detected, with a median VAF of 65.5% (range: 51.2-84.8). Subsequent confirmatory tests were performed for two PGPV, and the variants were confirmed to be of germline origin. Conclusions: VAF on ctDNA analysis can help to easily detect PGPV of hereditary breast cancer predisposition genes. The PGPV detected in ctDNA analysis should be validated by established germline tests, and the results could provide opportunities for targeted therapies, as well as cancer risk assessment of patients and their relatives.
Real-world effectiveness of prophylactic granulocyte colony-stimulating factor (G-CSF) early (week 1) and late (weeks 2-3) in the cycle for the prevention of febrile neutropenia (FN) among patients (pts) with breast cancer (BC) after high FN–risk chemotherapy (chemo).
Authors: Douglas W. Blayney, Alice Kate Cummings Joyner, John Jarvis, Dominic Nunag, Jasmine Wells, Lan Huang, Ramon W. Mohanlal
Journal: Journal of Clinical Oncology (2022)

599 Background: G-CSF mitigates chemotherapy-induced neutropenia (CIN) and reduces FN risk. G-CSF moves the nadir of absolute neutrophil count (ANC) earlier (to week 1) in the chemo cycle and shortens nadir duration (Crawford, NEJM 1991), suggesting the potential for suboptimal CIN protection early (week 1) in the chemo cycle. The relative FN risk in week 1 vs. weeks 2-3 of the cycle with G-CSF is unknown and was analyzed compared with no G-CSF in the real-world setting with high FN risk chemo. Methods: Using a database of administrative claims representing 100% of fee-for-service Medicare, we analyzed BC pts who initiated docetaxel (T), doxorubicin (A), or cyclophosphamide (C) monotherapy or combination therapy between 01/01/2015 – 12/31/2019. Sample pts included adults aged ≥ 65 years with continuous coverage in Medicare Parts A, B, and D for 6 months before and 20 days after chemo initiation. Pts were categorized as receiving vs. not receiving G-CSF therapy within 3 days after chemo. Rate of FN events starting in week 1 vs. weeks 2-3 in cycle 1 was calculated. We defined FN as an inpatient admission with a primary or secondary diagnosis of neutropenia and measured the interval between chemo initiation and FN admission. Results: Among 18,788 Medicare beneficiaries with BC treated with T, A, and/or C, 72% received G-CSF therapy. More pts receiving G-CSF were treated with ≥ 2 of T, A, and/or C compared to pts who did not receive G-CSF (71% vs. 51%). Overall FN incidence in cycle 1 was significantly lower among pts receiving G-CSF (4.0%; n=546) compared to pts not receiving G-CSF (8.8%; n=462) (p&lt;0.0001). In pts with G-CSF, 81% (440/546) of all 1 st -cycle FN events started in week 1 vs. 19% (106/546) in weeks 2-3. In pts not receiving G-CSF, the start of 1 st -cycle FN events was more equally distributed: 41% (190/462) started in week 1 vs. 59% (272/462) in weeks 2-3. Results were robust to sensitivity analyses restricted to pts receiving ≥ 2 of T, A, and/or C. The rates of 1 st -cycle FN events starting in weeks 1 and 2-3 with and without G-CSF following chemo initiation is shown below. Conclusions: Prophylactic G-CSF was highly effective for the prevention of FN in weeks 2-3, but relatively ineffective in week 1 of cycle 1 in the real-world setting, leaving pts largely unprotected during the first week. This represents an unmet medical need in week 1 of the cycle, despite use of G-CSF. Clinical trial information: NCT03294577. [Table: see text]
Therapy for patients with POD24 follicular lymphoma: Treatment patterns and outcomes from the Lymphoma Epidemiology of Outcomes (LEO) Consortium.
Authors: Carla Casulo, Melissa C. Larson, Jonathan R Day, Thomas Matthew Habermann, Izidore S. Lossos, Yucai Wang, Loretta J. Nastoupil, Christopher Strouse, Dai Chihara, Peter Martin, Jonathon Brett Cohen, Brad S. Kahl, Jia Ruan, Walter Richard Burack, Jean Louise Koff, Jonathan W. Friedberg, James Robert Cerhan, Christopher Flowers, Brian K. Link, Matthew J. Maurer
Journal: Journal of Clinical Oncology (2022)

7573 Background: While most patients (pts) with follicular lymphoma (FL) usually have favorable outcomes, those with refractory disease after first-line anti-CD20 based immunochemotherapy (IC), or progression within 24 months of diagnosis (POD24) have higher risk of premature death. There are no standard approaches for treating this vulnerable group and studies testing novel agents are ongoing in this setting. We sought to investigate clinical practice treatment choices and efficacy for pts with POD24 that align with eligibility criteria for the randomized SWOG1608 which compares IC with novel agents in this population. Methods: This was a multicenter observational cohort study from the LEO Consortium. Eligible pts had grade 1-3a FL diagnosed between 1/1/2002 and 2/1/2019, and initiated therapy after POD24 to first-line bendamustine or CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) based IC. Observation, radiotherapy, or rituximab monotherapy were permitted prior to IC and pts with transformation prior to the subsequent therapy after IC were excluded as per S1608. Outcomes of interest were overall and complete response rate (ORR/CR), progression-free survival (PFS), and overall survival (OS). Results: We identified 196 eligible pts with early progression to IC (39% antiCD20 Benda; 61% antiCD20 CHOP) who received subsequent therapy. Median age at post IC treatment was 57 years, 78% grade 1-2 FL. Treatments for pts with POD24 included CHOP- or Benda-based in 31%, salvage/hematopoietic stem cell transplant (HSCT) in 27%, novel therapies in 10% (including phosphatidylinositol 3-kinase inhibitors), antiCD20 monotherapy in 9%, and lenalidomide-based treatment in 8% (table); 21% of pts were treated on clinical trials. Across all treatments, ORR (CR) was 63% (37%) (95% CI: 55-70). At a median follow up of 6.2 years, 2 year PFS was 22% (95% CI: 17%-29%) and 5 year OS was 71% (95% CI: 65-79). Outcomes by regimen are shown in the table. Conclusions: Pts with FL experiencing POD24 following first-line IC are treated heterogeneously, with many pts still receiving IC as subsequent therapy. Despite modest CR rates and low 2-year PFS, 5-year OS appear to be improving compared to historical outcomes. This supports the ongoing need to investigate novel treatments in this population. [Table: see text]
Treatment patterns and time to next treatment among patients with OC in a real-life setting in Finland: The OCRWE-Finland study.
Authors: Heini Rauhamaa, Fredrik Herse, Outi Isomeri, Juhana Idänpään-Heikkilä, Sari Käkelä, Sakari Hietanen, Mikko Loukovaara, Annika Auranen
Journal: Journal of Clinical Oncology (2022)

e18806 Background: Ovarian cancer (OC) is a disease characterized by a dynamic treatment landscape in the real-life setting. The OCRWE-Finland study aims at describing the real-life burden of patients with OC, including treatment patterns, time to next treatment, disease characteristics and progression, survival, and healthcare resource utilization. This abstract reports on the observed treatment patterns. Methods: OCRWE-Finland is a multicenter, retrospective, noninterventional study collecting hospital medical records from the university hospitals in Helsinki, Turku, and Tampere. Patients with ovarian, fallopian tube, or primary peritoneal cancer who were newly diagnosed as part of routine clinical care and who received all their OC treatments in these university hospitals during the period 2014-2019 were included, covering about 50% of the Finnish OC care patients. Registry data were collected and combined by Findata (authorization holder), which operates under the performance guidance of the Finnish Ministry of Social Affairs and Health. Results: In total, 1711 patients with OC (mean age = 65.9 y, SD = 13.4 y) and 621 patients with high-grade serous OC (HGSOC) (mean age = 68.0 y, SD = 10.1 y) were identified. Initial diagnosis assumed the origin of the disease was the ovaries in 75% of patients and the peritoneum in 19%. Of the patients with HGSOC, 55% had FIGO stage III disease and 20% stage IV at diagnosis; 5% had stage II and 9% stage I. For 11%, no data of the FIGO stage at diagnosis were found in text mining. 59% of the HGSOC patients were treated with primary debulking surgery (PDS), 21% with neoadjuvant chemotherapy (CT) and interval debulking surgery, and 12% with only CT in first-line treatment (TL1). Among patients with stage I-IV HGSOC who underwent PDS, the disease was optimally debulked in 37% of the patients and suboptimally debulked in 44% (Residual &lt; 1 cm in 27%, Residual≥1 cm in 17%). Residual tumor status was unknown for 19%. During the observation period, 57% of patients received a TL2, and 48% of these patients moved to TL3. The probability of undergoing a TL2 was higher among stage III/IV patients and among patients with residual disease. In TL2, the most common treatment was platinum-based CT (32%), and “other CT” was administered in 26% of cases; 33% of patients did not receive any TL2 during the observation period but were still alive, and 9% died before initiating TL2. Conclusions: This study documents real-life treatment patterns across lines of treatment among patients with OC and HGSOC during the first years of disease from the three biggest university hospitals in Finland. These results can provide useful baseline information about the rapidly evolving treatment landscape in OC in recent years.
Tumor copy number alterations were associated with primary endocrine resistance in ER+ breast cancer.
Authors: Qianyi Lu, Fei Xu, Shusen Wang, Na Wang, Yang Shao, Yuming Ouyang
Journal: Journal of Clinical Oncology (2022)

e12567 Background: Several studies has showed alterations in genes were associated with endocrine resistance in breast cancer. Nevertheless, genomic landscape in primary endocrine-resistant breast cancer has not been thoroughly reported. Whether the genomic landscape of primary endocrine-resistant breast cancer is different from that of secondary endocrine-resistant breast cancer is unknown. Methods: We analyzed the genomic landscape of primary tumor of consecutive patients with estrogen-receptor positive (ER+) breast cancer in real-world clinical practice in our center between September, 2019 to December, 2020. According to the duration of endocrine treatment, we classified them into primary endocrine resistance group and secondary endocrine resistance group. Results: A total of 41 tumor samples of which 25 cases in primary endocrine resistance and 16 cases in secondary endocrine resistance were included for analysis. TP53 (65.9%, 27/41), PIK3CA (46.3%, 19/41), MYC (36.6%, 15/41), MCL1 (31.7%, 13/41), CCND1 (31.7%, 13/41) were the most frequently altered genes in all 41 BCs. Copy number amplification of MYC was common in primary endocrine resistant group (48.0%, 12/25), while lower in secondary endocrine resistant group (18.8%, 3/16, P = NS). Copy number alteration (CNA) of CCND1, MCL1, FGF19, ZNF217, ZNF703 and FGFR1 were commonly observed in primary endocrine resistance group. Percentage of CNA in all mutation types was significant increased in primary endocrine resistance group than in secondary resistance group (33.0% vs. 21.0%, P = 0.03). Then we further analyzed and found CNA burden, which was defined as number rather the percentage of the CNA event, was associated with the prognosis in ER+ breast cancer. When defining 6 as the cut-off value of CNA-High, DFS, PFS and OS were practically poorer in patients with CNA-High than those with CNA-Low. Conclusions: Copy number alterations were more commonly seen in primary endocrine-resistant breast cancer and associated with prognosis in ER+ breast cancer. This founding urged to further investigate the prognostic value of CNA burden in predicting the effectiveness of endocrine therapy.
RARE-23. Preservation of endocrine function after Ommaya reservoir insertion in children with cystic craniopharyngioma
Authors: Laura-Nanna Lohkamp, Abhaya V Kulkarni, James Drake, James T Rutka, Jill Hamilton, Ute K Bartels
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: Children with craniopharyngiomas (CP) can be subjected to significant morbidities caused by radical surgery and/or radiation with deleterious long-term consequences. Ommaya reservoir insertion (ORI) into cystic CP represents a minimally invasive procedure allowing immediate decompression and aims to avoid additional injuries. The purpose of this study was to determine the relevance of upfront ORI (+/- intracystic treatment) for preservation of endocrine function. METHODS: We performed a retrospective chart review of children with CP treated at the Hospital for Sick Children between 01/01/2000 and 15/01/2020 for review of endocrinological outcome after ORI. Endocrine function was reviewed at the time of initial surgery and throughout the course of follow-up. Event-free survival (EFS) was defined as the time to further surgical resection or irradiation. RESULTS: Seventy-nine patients were identified with a median age of 8.3 (range 2.1-18.0) years, 31 were males. Sixty-six patients underwent surgical treatment, including 41 ORI. ORI was performed as upfront treatment in 32 patients; 33 patients underwent gross total or partial resection and 1 patient radiotherapy as first treatment. Fifty-five of 79 patients had sufficient endocrine follow-up data. Endocrine function remained stable after ORI with a mean EFS of 27.64 (± 5.22) months. Surgical resection was associated with worsened endocrine function postoperatively with an EFS of 5.48 (± 1.74) months (p&amp;lt; 0.001). CONCLUSIONS: Upfront ORI (+/- intracystic treatment) resulted in endocrine preservation of all patients and a significantly longer EFS when compared to upfront surgical resection in this single institutional retrospective review. Further analyses will elucidate the implications of ORI with respect to ophthalmological, vascular and neurocognitive outcome.
Active Living After Cancer (ALAC) program: An avenue to improve physical functioning and moderate-intensity physical activity in gynecologic cancer survivors.
Authors: Jenna Unke, Jordan Wilson, Stacy J Mitchell, Giselle Montes, Karen Basen-Engquist, Nicole D. Fleming
Journal: Journal of Clinical Oncology (2022)

e24034 Background: Active Living After Cancer (ALAC) is a 12-week evidence-based program funded by the Cancer Prevention and Research Institute of Texas (CPRIT) to provide physical activity and survivorship education to cancer survivors. Given the limited data evaluating the effects of physical activity educational programs in gynecologic cancer survivors, we aim to assess the effects of the ALAC intervention in this patient population. Methods: A retrospective analysis was performed on gynecologic cancer survivors who participated in ALAC from 2017 to 2021. The 12-week ALAC program included weekly meetings (in-person or virtual) led by a facilitator providing physical activity behavioral skills training, leading 10 minutes of exercise, and discussing topics related to cancer survivorship. Surveys and functional testing assessments were collected pre- and post-program which included: The Godin-Shephard Leisure-Time Physical Activity Questionnaire (GSLTPAQ) and 30-second sit-to-stand. A patient-reported outcomes survey was used to assess patient perceived benefits and program satisfaction. Results: Thirty-two patients participated in ALAC and 22 completed pre- and post-program assessments. The mean age of participants was 60.2 years (range 50.7-69.7 years) and mean number of classes attended was 8 (range 0-12 classes). Prior cancer diagnoses included 14 cervical, 11 uterine, and 7 ovarian cancers. A significant improvement was seen pre- and post-ALAC in moderate-intensity physical activity minutes (n = 17, 97 vs 252 minutes, p = 0.007) by GSLTPAQ and 30-second sit-to-stand test (n = 16, 12.3 vs 15.8 repetitions, p = 0.003) in our cohort. The post-ALAC patient reported outcome survey (n = 22) revealed improvement in emotional well-being (90%), physical well-being (91%), physical activity level (100%), comfort speaking openly in a group (85%), and willingness to discuss their cancer journey (66%). Overall, 95.3% of participants were satisfied with the ALAC program and 100% of participants would recommend the ALAC program to other cancer survivors. Conclusions: Educational physical activity-based programs like ALAC improve physical functioning and moderate-intensity physical activity in gynecologic cancer survivors. Further studies on the long-term health benefits of structured educational programs which promote active lifestyles in gynecologic cancer survivors are needed in larger patient cohorts.
A multicenter cohort of patients treated with concurrent chemoradiotherapy for muscle invasive bladder carcinoma: Results of the past 10 years
Authors: B. De Ruiter, M.W. Van De Kamp, J.P.Z. Van Steenbergen, M. Franckena, J.L. Boormans, J.M. De Feijter, A.D. Bins, M.C.C.M. Hulshof, T.M. De Reijke, E. Schaake, J.R. Oddens
Journal: European Urology (2022)